Dr Winter on Unmet Needs in Richter Transformation for Patients With CLL

Allison Winter, MD, Department of Hematology and Medical Oncology, Cleveland Clinic, discusses unmet needs for patients with Richter transformation from chronic lymphocytic leukemia (CLL), highlighting the rationale for conducting a retrospective analysis evaluating real-world outcomes with lisocabtagene maraleucel (liso-cel; Breyanzi) in this patient population.

, investigators presented these real-world findings in patients with Richter transformation, which were gathered from the Center for International Blood and Marrow Transplant Research (CIBMTR). The study included 30 patients and found that liso-cel elicited high overall response rates (ORRs) with deep and durable responses and no new safety signals. The median time from CLL diagnosis to Richter transformation was 49 months (range, 0-180), and the median time from Richter transformation to liso-cel infusion was 11 months (range, 1-110). Results showed a 76% ORR (95% CI, 56.5%-89.7%) and a 66% complete response rate (95% CI, 45.7%-82.1%) among evaluable patients, with a median follow-up of 12.3 months (95% CI, 6.1-12.5). The median progression-free survival and overall survival (OS) were not reached (NR; PFS 95% CI, 3.0-NR; OS 95% CI, 10.4-NR), but the estimated 1-year OS rate was 67% (95% CI, 43.6%-82.8%).

Richter transformation is a rare but serious complication that can arise in patients with CLL, occurring in 1% to 10% of cases, depending on the source, Winter begins. There is no established standard of care for this patient population, leading to a significant unmet need due to the poor outcomes, with median OS outcomes ranging from 3 to 12 months, she explains. Effective and durable therapies are urgently needed, Winter reports.

Winter continues by stating that the rationale for this study was to evaluate liso-cel infusion in patients with Richter transformation, she expands. Investigators aimed to specifically assess this population, excluding those with diffuse large B-cell lymphoma not associated with Richter transformation, to gain insights into the effectiveness and safety of this treatment, Winter shares. This multicenter study used real-world data from the CIBMTR, examining the commercial use of liso-cel in patients who received a single infusion and had at least 6 months of follow-up before the data cutoff in February 2023, Winter concludes.

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Allison Winter, MD, discusses unmet needs for patients with Richter transformation from CLL.

Dr Winter on Real-World Outcomes With Liso-Cel in Richter Transformation

Allison Winter, MD, Department of Hematology and Medical Oncology, Cleveland Clinic, discusses findings from a retrospective analysis evaluating real-world outcomes with lisocabtagene maraleucel (liso-cel; Breyanzi) in patients with Richter transformation and the clinical implications of these results.

, Winter presented findings from a multicenter, observational study investigating the real-world outcomes of patients with Richter transformation enrolled in the Center for International Blood and Marrow Transplant Research Cellular Therapy registry who received treatment with liso-cel from February 5, 2021, through August 4, 2023. At a median follow-up of 12.3 months (95% CI, 6.1-12.5), liso-cel elicited an overall response rate of 76% (n = 22; 95% CI, 56.5%-89.7%), including a complete response rate of 66% (n = 19; 95% CI, 45.7%-82.1%). The median time to first response was 1.1 months (range, 0-3.1).

Patients who responded to liso-cel had durable responses, Winter says. The median duration of response (DOR) was not reached (NR; 95% CI, 5.6 months-NR), and the 12-month DOR rate was 77% (95% CI, 49.5%-91.0%). Furthermore, the median overall survival (OS) was NR (95% CI, 10.4%-NR), and the 6- and 12-month OS rates were 79% (95% CI, 59.2%-90.1%) and 67% (95% CI, 43.6%-82.8%), respectively. The median progression-free survival (PFS) was NR (95% CI, 3.0 months-NR), and the 6- and 12-month PFS rates were 65% (95% CI, 44.8%-79.5%) and 54% (95% CI, 32.7%-71.6%), respectively.

Although many patients with Richter transformation are treated with chemoimmunotherapy, no standard of care exists for this population, Winter emphasizes. Furthermore, many patients do not respond to treatment or relapse soon after achieving a response, Winter notes. Therefore, the durable efficacy of liso-cel in this patient population was encouraging, especially since liso-cel is a commercially available product that requires a single infusion, Winter explains. Future research efforts may evaluate liso-cel–based combination regimens in this patient population, Winter concludes. 

Allison Winter, MD, discusses data from a retrospective analysis evaluating real-world outcomes with liso-cel in patients with Richter transformation.

Allison Winter, MD, hematologist/medical oncologist, Cleveland Clinic, discusses emerging agents in chronic lymphocytic leukemia (CLL).

The pipeline of CLL is rich with investigational combination strategies, says Winter. In addition to safety and efficacy findings, minimal residual disease data may be used to determine which of these combinations will be optimal for patients.

Additionally, novel PI3K inhibitors are emerging in this space and appear to elicit less immune-related adverse effects compared with currently approved PI3K inhibitors, Winter explains. The BTK inhibitor LOXO-305 is another intriguing agent because it can overcome BTK inhibitor resistance. For example, LOXO-305 or potentially CAR T-cell therapy could have utility for heavily pretreated patients who received prior bendamustine and rituximab (Rituxan), ibrutinib (Imbruvica), idelalisib (Zydelig), and venetoclax (Venclexta), concludes Winter. 

Allison Winter, MD, discusses emerging agents in chronic lymphocytic leukemia.  


Dr. Winter on Emerging Agents in CLL 

Allison Winter, MD, hematologist/medical oncologist, Cleveland Clinic, discusses the role of frontline targeted therapies in chronic lymphocytic leukemia (CLL).

Historically, when it came to frontline treatment selection for patients with CLL, factors such as fluorescence in situ hybridization scores andimmunoglobulin heavy chain results played important roles; however, now that the CLL space is shifting away from the use of chemotherapy, this is no longer the case, Winter says.

Notably, as targeted therapies continue to take the stage in the CLL treatment paradigm, only younger patients with an 

-mutated status, who do not harbor 17p or 11q deletions, are being considered for frontline chemotherapy. The majority of patients with CLL, including those with high-risk disease, are now being treated with targeted therapies, Winter explains.

With the number of targeted therapies available, patient preference is critical. Gaining a deeper understanding of the patient’s life, along with what is important to them, is of paramount importance, especially in terms of optimizing their quality of life, Winter concludes.

Allison Winter, MD, hematologist/medical oncologist, Cleveland Clinic, discusses the role of frontline targeted therapies in chronic lymphocytic leukemia. 








Dr. Winter on the Role of Frontline Targeted Therapies in CLL

Allison Winter, MD, hematologist/medical oncologist, Cleveland Clinic, discusses the utility of PI3K inhibitors in chronic lymphocytic leukemia (CLL).

Patients who have progressed on prior BTK inhibitor therapy and venetoclax (Venclexta)-based therapy should be considered for a PI3K inhibitor as standard of care or within the context of a clinical trial, says Winter.

Investigational PI3K inhibitors, such as zandelisib (ME-401), are being evaluated in ongoing clinical trials for patients with relapsed/refractory CLL. Moreover, the agent appears to have a more favorable immune-related toxicity profile compared with approved PI3K inhibitors, such as idelalisib (Zydelig) and duvelisib (Copiktra), Winter explains. Additionally, the PI3K inhibitor umbralisib is being tested in combination with other agents in a number of ongoing clinical trials in this space, concludes Winter.

Allison Winter, MD, discusses the utility of PI3K inhibitors in chronic lymphocytic leukemia.  



Allison Winter, MD

Articles

Dr Winter on Unmet Needs in Richter Transformation for Patients With CLL

Dr Winter on Real-World Outcomes With Liso-Cel in Richter Transformation

Dr. Winter on Emerging Agents in CLL

Dr. Winter on the Role of Frontline Targeted Therapies in CLL

Dr. Winter on the Utility of PI3K Inhibitors in CLL